Specific Aim 1 of the Clinical Core is to recruit, screen and enroll into research protocols subjects from defined populations, to follow participants prospectively, maintaining close adherence to study procedures, to obtain clinical specimens required for virologic and immunologic laboratory investigations. We will focus on enrolling a) participants with both HSV-2 and HIV infection to address the specificaims of Project 1 and Laboratory Core, and b) participants with primary genital HSV-2 infection to address the specific aims of Project 3 and Laboratory Core. Specific Aim 2 is to develop and maintain a database of demographic, clinical and virologic characteristics of various populations with and without HSV infection. To develop and maintain a collection of host genomic DNA samples from participants with and without HSV infection for investigations related to genetic determinants of HSV susceptibility and severity, such as DNA polymorphism of HSV receptor, HLA allele, and nk receptor locus and cytokine genes. To develop and maintain a collection of viral strainsfrom HSV-1 and HSV-2 infected persons for studies of susceptibility of re-infection with new strains, and viral factors associated with virulence. The Core is located at the University of Washington Virology Research Clinic (VRC). The VRC was founded in 1974 as a center for studies of natural history and therapeutics of HSV infections. The clinic has followed >1000 persons with first episode of genital herpes and >3400 persons with recurrent HSV-2 infection. In the last 10 years, 245 HIV seropositive persons with HSV infection have also been prospectively followed. Techniques used in the evaluation of study participants include daily home swab collection for viral culture and PCR. Other procedures include biopsies of genital lesions and normal skin, rectal and cervical biopsies, UV light induction of genital herpes recurrences, and leukapheres is for detailed virologic and immunologic studies of host-virus interactions. Both host and viral genomic DNA of participants in the detailed virologic and immunologic studies is stored for future investigations of genetic determinants of HSV susceptibility, resistance and disease severity.